We propose two studies with the aim of better understanding the role of inhibited functional brain activity (assessed by regional cerebral blood flow [rCBF]) and abnormal pain perception in the etiopathogenesis of fibromyalgia (FM). To accomplish this aim, we will test six hypotheses based on an etiopathogenetic model of FM developed in our laboratory. Specifically, we wish to determine whether: (a) functional brain activity in the thalamus and caudate nucleus during resting conditions and behavioral indices of pain perception reliably distinguish FM patients from patient with chronic fatigue syndrome (CFS) or major depression and healthy controls; and (b) FM patients differ from the three comparison groups with respect to changes in functional brain activity in the thalamus, caudate nucleus, appropriate somatosensory cortices, and anterior cyngulate gyrus upon exposure to painful dolorimeter stimulation. We will recruit (a) 30 patients with primary FM by American College of Rheumatology (ACR) criteria; (b) 30 patients with CFS by Centers for Disease Control criteria who are pain-free and do not meet ACR criteria for FM; (c) 30 patients with current major depression who are pain-free and do not meet criteria for other current psychiatric diagnoses or criteria for FM or CFS; and (d) 30 healthy controls who are pain-free and do not meet criteria for FM or CFS. Patients will be recruited from appropriate UAB outpatient clinics and controls will be recruited from the Birmingham community. All subjects will be right-handed women. We propose to measure (a) pain thresholds for dolorimeter stimulation of 5 paired ACR tender points as well as behavioral indices of sensory discrimination ability and response bias; (b) rCBF using single photon emission computed tomographic (SPECT) imaging; and (c) responses to questionnaire measures of anxiety, depression, and pain as well as a structured psychiatric interview. The proposed studies represent an advance in the study of FM since they include the use of an experimental manipulation as well as correlational studies to evaluate an etiopathogenetic model of FM. The results also will help us to better understand the mechanisms responsible for inhibited functional brain activity observed in FM patients during resting conditions.